Immune System Component Found Common to Both Humans and Worms

When someone gets a bacterial infection, the human body mounts a complex set of reactions aimed at destroying the invader. The role of what is called the innate immune system -- one of the most basic aspects of the overall immune response -- is to sound the alarm and jump start the body's response to pathogens. Researchers have known that key components of innate immunity are conserved across a variety of animals, and now scientists at Massachusetts General Hospital (MGH) have shown that these same elements are used by the lowly worm as well. The findings, published in the July 26 issue of Science, suggest that scientists will now be better able to tease out the details of innate immunity across a wide range of species.

"Innate immunity plays a central role in the initial encounter with foreign pathogens and is thus critical to the host's defense against infection," says co-lead author Dennis Kim, MD, PhD, of the MGH Department of Molecular Biology. "But derangement of the innate immune system is implicated in the pathogenesis of overwhelming infections, as well as in chronic inflammatory diseases. We anticipate that learning about fundamental aspects of the innate immune system may lead to therapies for these conditions." Because innate immunity is conserved among most animals, scientists have been studying it in the laboratory using insect models. This new report gives researchers another tool.

"The C. elegans nematode worm is more primitive than an insect, and it's an excellent model organism that has provided scientists with insights into development and other basic biological processes. We hope that our study provides the basis for now using the worm to study immune function," says principal investigator Frederick Ausubel, PhD, of the MGH Department of Molecular Biology.

Ausubel's team has previously noted that human pathogens, such as certain bacteria, can also kill C. elegans. So Ausubel, Kim and co-lead author Rhonda Feinbaum, PhD, also of MGH, set out to determine whether the immune responses of these two organisms were similar. To do that, they looked for worms that were immunocompromised or extra-susceptible to pathogens. They identified two genetic mutations associated with this susceptibility in genes that are part of a signaling pathway also known to be involved in the innate immune response of humans.

"Because it's the only known component of the immune system common to both C. elegans and humans, this pathway probably represents the most ancient aspect of innate immunity," says Ausubel. "So our results validate the use of C. elegans to study innate immunity, and insights gained from the study of this pathway certainly will have human applications."

Kim says using the worm as a laboratory model for innate immunity will not replace the utility of insect models. "Insects have been very important in providing insights into innate immunity," he says. "We anticipate that the study of C. elegans immunity will provide additional insights."

Other co-authors of the paper are Genevieve Alloing, PhD, Fred Emerson, Danielle Garsin, PhD, and Man-Wah Tan, PhD, of the MGH Department of Molecular Biology, and Hideko Inouo, Miho Tanaka-Hino, Naoki Hisamoto, PhD, and Kunihiro Matsumoto, PhD, of Nagoya University in Japan. The study was supported by grants from the National Institutes of Health and from Advanced Research on Cancer of the Ministry of Education, Culture, and Science of Japan.

The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women's Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.